title: Time-course of sFlt-1 and VEGF-A release in neutropenic patients with sepsis and septic shock: a prospective study.
abstract: BACKGROUND
  Septic shock is the most feared complication of chemotherapy-induced febrile neutropenia. So far, there are no robust biomarkers that can stratify patients to the risk of sepsis complications. The VEGF-A axis is involved in the control of microvascular permeability and has been involved in the pathogenesis of conditions associated with endothelial barrier disruption such as sepsis. sFlt-1 is a soluble variant of the VEGF-A receptor VEGFR-1 that acts as a decoy receptor down-regulating the effects of VEGF-A. In animal models of sepsis, sFlt-1 was capable to block the barrier-breaking negative effects of VEGF-A and to significantly decrease mortality. In non-neutropenic patients, sFlt-1 has been shown to be a promising biomarker for sepsis severity.
  
  
  METHODS
  We prospectively evaluated concentrations of sFlt-1 and VEGF-A at different time-points during febrile neutropenia, and evaluated the association of these levels with sepsis severity and septic shock development.
  
  
  RESULTS
  Neutropenic patients that evolved with septic shock (n = 10) presented higher levels of sFlt-1 and VEGF-A measured 48 hours after fever onset than patients with non-complicated sepsis (n = 31) and levels of these biomarkers correlated with sepsis severity scores. Estimation of the diagnostic accuracy of sFlt-1 levels for the discrimination of patients that evolved to septic shock yielded promising results in our study population.
  
  
  CONCLUSIONS
  Our data suggest that sFlt-1 and VEGF-A could be useful biomarkers for sepsis severity in patients with febrile neutropenia. In addition, the kinetics of sFlt-1 release in patients that evolve to septic shock suggest that the sFlt-1 could be a salvage compensatory mechanism in patients with septic shock, but that the magnitude of the sFlt-1 release observed in human sepsis is not sufficient to reproduce the beneficial anti-VEGF-A effects observed in animal models of sepsis.
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas, Campinas, SP, Brazil.
authors.forename: Brunna E
authors.initials: BE
authors.lastname: Alves
authors.forename: Silmara A L
authors.initials: SA
authors.lastname: Montalvao
authors.forename: Francisco J P
authors.initials: FJ
authors.lastname: Aranha
authors.forename: Irene
authors.initials: I
authors.lastname: Lorand-Metze
authors.forename: Carmino A
authors.initials: CA
authors.lastname: De Souza
authors.forename: Joyce M
authors.initials: JM
authors.lastname: Annichino-Bizzacchi
authors.forename: Erich V
authors.initials: EV
authors.lastname: De Paula
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000097:blood / Q000150:complications*; D011379:Prognosis; D011446:Prospective Studies; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood / Q000378:metabolism*; D055815:Young Adult
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1